A Study To Investigate The Pharmacokinetics, Safety And Tolerability Of An Intravenous And Oral Form Of A Compound In Subjects With Varying Degrees Of Renal Impairment And Normal Renal Function

AUC (0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

AUC (0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Area under the plasma concentration time-curve from zero (pre-dose) to the time of last measured concentration (AUClast).

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Area under the plasma concentration time-curve from zero (pre-dose) to the time of last measured concentration (AUClast).

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

PF-03709270 is an oral prodrug of CP-70,429. Upon oral absorption, PF-03709270 is rapidly hydrolyzed, yielding the active drug CP-70,429. Cmax of CP-70429 following CP-70,429 intravenous dose was reported.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The pharmacokinetic (PK) parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

PF-03709270 is an oral prodrug of CP-70,429. Upon oral absorption, PF-03709270 is rapidly hydrolyzed, yielding the active drug CP-70,429. Cmax of CP-70429 following CP-70,429 intravenous dose was reported.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The pharmacokinetic (PK) parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).

Time frame: 0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).

Time frame: 0 (pre-dose), 0 to 6, 6 to 12, 12 to 24 hours post-dose

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing the given oral dose by AUCinf. AUC inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing given intravenous dose by AUC inf. AUC inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ =100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.

Time frame: 1, 3, 8 hours post-dose

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ =100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.

Time frame: 1, 3, 8 hours post-dose

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Duration was calculated by subtracting the time at which the plasma concentrations exceeded 0.5 microgram per milliliter (mcg/mL) at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 0.5 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Duration was calculated by subtracting the time at which the plasma concentrations exceeded 0.5 mcg/mL at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 0.5 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Duration was calculated by subtracting the time at which the plasma concentrations exceeded 1.0 mcg/mL at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 1.0 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Duration was calculated by subtracting the time at which the plasma concentrations exceeded 0.5 mcg/mL at the ascending part of the concentration-time profile from the time at which the plasma concentrations fell below 0.5 mcg/mL at the descending part of the profile. If these times fell between 2 observed concentrations, a method of linear interpolation was used for best estimation.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Criteria for abnormal ECG (12-lead) values were defined as: maximum PR interval \>=300 millisecond (msec) and maximum increase of \>=25 percent for baseline value of \>200 msec and \>=50% for baseline value of \<=200 msec for PR interval, QRS interval \>=200 msec; QT interval corrected using the Fridericia formula (QTcF) \>=500 msec or increase of \>45 msec.

Time frame: Baseline up to 7-10 days after the last dose of study drug (up to 32 days)

Population: Safety analysis set included all participants who received the study medication.

Physical examination included examination of the skin, eyes, ears, throat, neck, and cardiac, respiratory, gastrointestinal and musculoskeletal systems. The examination assessed the participants for any potential changes in physical status, as determined by the investigator. Any untoward findings identified on physical exams conducted after the administration of the first dose of study medication was captured as an adverse event.

Time frame: Baseline, 7-10 days after the last dose of study drug

Population: Safety analysis set included all participants who received the study medication.

Criteria for laboratory test abnormality: Hematology (hemoglobin, hematocrit, red blood corpuscles \[RBC\] count: less than \[\<\]0.8\*lower limit of normal \[LLN\], platelets: \<0.5\*LLN/greater than \[\>\]1.75\*upper limit of normal \[ULN\], leukocytes: \<0.6\*LLN or \>1.5\*ULN, lymphocytes, total neutrophils: \<0.8\*LLN or \>1.2\*ULN, basophils, eosinophil, monocytes: \>1.2\*ULN); Liver Function (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: \>0.3\*ULN, total protein, albumin: \<0.8\*LLN or \>1.2\*ULN); total bilirubin, direct bilirubin, indirect bilirubin: \>1.5\*ULN; Renal Function (blood urea nitrogen, creatinine: \>1.3\*ULN, uric acid: \>1.2\*ULN); Electrolytes (sodium: \<0.95\*LLN or \>1.05\*ULN, potassium, chloride, calcium, bicarbonate: \<0.9\*LLN or \>1.1\*ULN; creatine kinase: \>2.0\*ULN; glucose fasting: \<0.6\*LLN or \>1.5\*ULN, urine white blood corpuscles \[WBC\] and RBC: greater than or equal to (\>=) 6/High Power Field \[HPF\]).

Time frame: Baseline up to 7-10 days after the last dose of study drug (up to 32 days)

Population: Safety analysis set included all participants who received the study medication.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 7-10 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

Time frame: Baseline up to 7-10 days after the last dose of study drug (up to 32 days)

Population: Safety analysis set included all participants who received the study medication.

Criteria for vital signs abnormalities included supine/sitting pulse rate of \<40 beats per minute (bpm) or \>120 bpm, supine systolic blood pressure (SBP) of \<90 millimeter of mercury (mmHg), \>=30 mmHg maximum increase and decrease from baseline in same posture, supine diastolic blood pressure (DBP) of \<50 mmHg, \>=20 mmHg maximum increase and decrease from baseline in same posture, heart rate \<=45 beats per minute (bpm) or \>=120 bpm or decrease/increase of \>=15 bpm.

Time frame: Baseline up to 7-10 days after the last dose of study drug (up to 32 days)

Population: Safety analysis set included all participants who received the study medication.

PF-03709270 is an oral prodrug of CP-70,429. Upon oral absorption, PF-03709270 is rapidly hydrolyzed, yielding the active drug CP-70,429 and metabolites.

Time frame: 0.5, 2, 4, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: Data was not collected for this outcome because the metabolite data for CP-70,429 and PF-03709270 were not analyzed as per change in planned analysis

Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half.

Time frame: 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment)

Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.